Plasma lipoproteins and apolipoproteins in insulin-dependent and young non-insulin-dependent Arab women

Summary Plasma lipids, lipoproteins and apolipoproteins (apo) were analysed in 30 young Arab IDDM and 50 young insulin-requiring NIDDM women. The mean age of IDDM and NIDDM groups was 20.2 and 34.5 years, and mean duration of diabetes was 5.7 and 4.6 years, respectively. Two groups of 40 and 60 healthy women (matched for age and BMI) provided corresponding control groups. In comparison with control subjects, diabetics showed marked increases in the following parameters: total cholesterol (TC), low density lipoprotein (LDL) cholesterol, total triglycerides (TG), very low density lipoprotein (VLDL) triglycerides, phospholipids, apoB, LDL apoB, glucose and glycosylated hemoglobin (HbA_1c) as well as the ratios of total cholesterol/high density lipoprotein (HDL) cholesterol, LDL-cholesterol/HDL-cholesterol, LDL cholesterol/high density lipoprotein 2 (HDL₂) cholesterol and apoB/apoAI. Plasma LCAT activity, concentrations of HDL₃ apoAI and apoAII in plasma and lipoprotein fractions were normal in both the diabetic groups. Levels of C-peptide, HDL, HDL₂ and HDL₃ cholesterol, plasma apoAI, HDL apoAI and HDL₂ apoAI were markedly decreased in the diabetic groups as compared to their corresponding controls. There was no significant correlation between fasting glucose or HbA_1c and any of the above parameters. Despite insulin therapy in both the diabetic groups studied, abnormalities in lipids, apoB and apoAI still persisted. Our data suggest a possible higher risk of atherosclerosis in these patients.     

Relationship between plasma phospholipid transfer protein activity and HDL subclasses among patients with low HDL and cardiovascular disease

Low levels of high density lipoproteins (HDL) are associated with an increased risk for premature cardiovascular disease. The plasma phospholipid transfer protein (PLTP) is believed to play a critical role in lipoprotein metabolism and reverse cholesterol transport by remodeling HDL and facilitating the transport of lipid to the liver. Plasma contains two major HDL subclasses, those containing both apolipoproteins (apo) A-I and A-II, Lp(A-I, A-II), and those containing apo A-I but not A-II, Lp(A-I). To examine the potential relationships between PLTP and lipoproteins, plasma PLTP activity, lipoprotein lipids, HDL subclasses and plasma apolipoproteins were measured in 52 patients with documented cardiovascular disease and low HDL levels. Among the patients, plasma PLTP activity was highly correlated with the percentage of plasma apo A-I in Lp(A-I) (r=0.514, p<0.001) and with the apo A-I, phospholipid and cholesterol concentration of Lp(A-I) (r=0.499, 0.478, 0.457, respectively, p≤0.001). Plasma PLTP activity was also significantly correlated with plasma apo A-I (r=0.413, p=0.002), HDL cholesterol (r=0.308, p=0.026), and HDL₂ and HDL₃ cholesterol (r=0.284 and 0.276, respectively, p<0.05), but no significant correlation was observed with Lp(A-I, A-II), plasma cholesterol, triglycerides, or apo B, very low density lipoprotein cholesterol or low density lipoprotein cholesterol. These associations support the hypothesis that PLTP modulates plasma levels of Lp(A-I) particles without significantly affecting the levels of Lp(A-I, A-II) particles.     

Deficiency of Hepatic Lipase Activity in Post-heparin Plasma in Familial Hyper-α-Triglyceridemia

ABSTRACT. Hyper-α-triglyceridemia is a rare dyslipoproteinemia characterized by a pronounced increase in the concentration of triglycerides in the plasma high density lipoprotein (HDL) fraction. One case with this condition, an apparently healthy 61-year-old man, has been studied. Additional lipoprotein abnormalities were present, such as abnormally cholesterol-rich very low density lipoproteins (VLDL) with retarded electrophoretic mobility (β-VLDL) and triglyceride enrichment of low density lipoproteins-(LDL). The patient's plasma concentration of apolipoproteins A-I, A-II and B were normal and those of C-I, C-II, C-III and E were elevated. No abnormal forms of the soluble apolipoproteins of VLDL and high density lipoproteins (HDL) were found after analysis by isoelectric focusing. Lecithin: cholesterol acyltransferase activities, plasma cholesterol esterification rates and lipid transfer protein activities were normal. Post-heparin plasma activity of hepatic lipase was virtually absent and that of lipoprotein lipase was reduced by 50%. In plasma of this patient, HDL was almost exclusively present as large triglyceride-rich particles corresponding in size to particles of the HDL₂ density fraction. The only brother of the patient also had hyper-α-triglyceridemia together with the other lipoprotein abnormalities described for the index case and deficiency of postheparin plasma activity of hepatic lipase. The findings presented below support the hypothesis that one primary function of hepatic lipase is associated with degradation of plasma HDL₂. Deficiency of this enzyme activity thus causes accumulation of HDL₂ in plasma leading to hyper-α-triglyceridemia. The results further suggest that the abnormal chemical and electrophoretic properties of VLDL and LDL in plasma from the patient, reminiscent of type III hyperlipoproteinemia, are secondary to the lack of the action of hepatic lipase on the HDL particles.     

Lipoprotein compositional abnormalities in type 1 (insulin-dependent) diabetic patients

Patients with type 1 (insulin-dependent) diabetes mellitus in good metabolic control usually have normal plasma lipid levels yet they have an increased incidence of vascular complications. Abnormalities in the distribution and composition of lipoprotein subfractions might in part be responsible for the macroangiopathy seen in type 1 diabetes mellitus. The plasma lipids, lipoproteins and apolipoproteins were studied in 9 type 1 diabetic patients during conventional insulin therapy and in 14 healthy controls. Plasma lipoproteins were analysed by ultracentrifugation in a zonal rotor to evaluate their concentrations and flotation properties and for compositional analysis. In diabetic patients the mean glycosylated haemoglobin (HbA_1c) was 9.44±1.02% and the plasma lipid concentrations were not significantly different from healthy controls. The very low density lipoprotein (VLDL) subclass cholesterol concentrations were no different in diabetic patients and control subjects, but the VLDL cholesterol/triglyceride ratio was significantly lower in diabetic patients than in control subjects (0.34±0.05 vs 0.85±0.14; p<0.05). The flotation rate of LDL₂, the major component of low density lipoprotein (LDL) was lower in the diabetic patients compared with the control subjects. The cholesterol concentrations of intermediate density lipoprotein and LDL₃, the minor component of LDL, were significantly higher (0.17±0.03 and 0.83±0.14 mmol/l respectively) in diabetic patients than in control subjects (0.05±0.02 and 0.24±0.08 mmol/l). The flotation properties and cholesterol concentrations of the high density lipoprotein (HDL) subclass, and the protein-lipid composition of LDL₂, HDL₂ and HDL₃, were no different in diabetic patients and control subjects. Diabetic patients had lower apoprotein AII and higher CII and E levels than control subjects. the plasma lipoproteins in type 1 diabetes mellitus are characterized by increased intermediate density lipoprotein and LDL₃ concentrations and by abnormal LDL₂ flotation properties. These lipoprotein abnormalities might have a role in atherogenesis in type 1 diabetic patients since similar alterations were associated in some recent epidemiological studies with an increased incidence of cardiovascular disease in non-diabetic patients.     

Effects of transdermal 17β-oestradiol combined with oral progestogen on lipids and lipoproteins in hypercholesterolaemic postmenopausal women

Abstract. Objectives. The purpose of the study was to evaluate the effect of transdermal 17β-oestradiol with oral progestogen on the plasma levels of lipids, lipoproteins and apolipoproteins in hypercholesterolaemic postmenopausal women. Design. During 6 months of replacement therapy with transdermal 17β-oestradiol combined with oral progestogen, plasma lipids, lipoproteins and apolipoproteins after 3 and 6 months were measured and compared with pretreatment values by Student's t-test. Setting. From January 1992 until September 1992 patients were diagnosed and treated in an outpatient clinic of the Department of Endocrinology Medical Centre for Postgraduate Education, Warsaw. Subjects. The patients studied were 11 non-obese postmenopausal women with hypercholesterolaemia based on the World Health Organization criteria. Interventions. Venous blood samples were obtained before and 3 and 6 months after the beginning of cyclic replacement therapy with transdermal 17β-oestradiol (E2 100 μg day^?1 combined with oral chlormadinone acetate (2 mg day^?1 for 7 days in each cycle). Main outcome measures. The antiatherogenic effect of transdermal oestrogen replacement therapy exerted by increased levels of high-density lipoprotein sub-fraction 2 cholesterol (HDL₂-C) leading to the decrease of the total cholesterol level was anticipated. Results. After 6 months of the treatment the concentrations of HDL₂ cholesterol (HDL₂-C) increased from 0.45 ± 0.07 mmol l^?1 to 0.73 ± 0.03 mol l^?1 (P < 0.05) but the levels of HDL₃ cholesterol (HDL₃-C) decreased from 1.15 ± 0.06 mmol l^?1 to 0.89 ± 0.07 mmol l^?1 (P < 0.05). The concentrations of total cholesterol decreased from 6.9 ± 0.13 mmol l^?1 to 6.2 ± 0.2 mmol l^?1 (P < 0.05). No changes were observed in the plasma levels of total triglycerides, HDL cholesterol, low-density lipoprotein (LDL) cholesterol, very-low-density lipoprotein (VLDL) cholesterol, VLDL triglycerides, apolipoproteins A-I and B. Conclusions. In hypercholesterolaemic postmenopausal women, transdermally administered 17β-oestradiol 100 μg daily in combination with oral chlormadinone acetate has a beneficial effect through raising the level of the antiatherogenic HDL₂-C subfraction and decreasing the level of total cholesterol.     

Heterogeneity of human high density lipoprotein: Presence of lipoproteins with and without apoE and their roles as substrates for lecithin:cholesterol acyltransferase reaction

By affinity chromatography on heparin-Sepharose, two classes of lipoproteins were separated from high density lipoproteins (HDL) isolated from patients with primary or secondary lecithin:cholesterol acyltransferase (LCATase; EC 2.3.1.43) deficiency and from normal subjects. The unretained fraction, HDL_A, was characterized by having apoA-I as a major apoprotein; it also contained apoA-II, -C-II, and -C-III but it contained only traces of immunodetectable apoE and no apoB. The retained fraction, HDL_E, had apoE as the major apoprotein; it also contained apoA-I, -A-II, -B, -C-II, and -C-III. The relative concentration of apoA-I increased with increasing density in the HDL_E subclass. Compared to HDL_A, HDL_E had a significantly higher cholesterol content and a lower protein concentration. HDL_E was mainly (90%) contained within the HDL₂ subfraction. Contamination of HDL_E by low density lipoproteins (LDL) or Lp(a) was minimal on the basis of pre-β-electrophoretic mobility and absence of albumin, respectively. Contamination by LDL or Lp(a) could be resolved in part by application of HDL_E to concanavalin A-Sepharose or to heparin-Sepharose with a shallow gradient. When evaluated as substrates for a highly purified LCATase preparation, the initial reaction rates and V_max obtained with HDL_A were always higher than those obtained with HDL_E in any given plasma. However, both HDL subclasses from LCATase-deficient subjects were better substrates than the corresponding HDL subclasses from normal plasma. Also, both HDL_3A and HDL_3E isolated from normal HDL₃ were better substrates than the corresponding subclasses isolated from normal HDL₂. The recognition of this compositional and functional heterogeneity within HDL will allow a better understanding of the metabolism of this lipoprotein class.     

High density and low density lipoprotein subfractions in survivors of myocardial infarction and in control subjects

The major lipoprotein classes (very low, low and high density lipoproteins, VLDL, LDL and HDL) and three lipoprotein subfractions (HDL₂, HDL₃ and LDL₂) of 31 male survivors of myocardial infarction (MI) have been compared with those of 24 ostensibly normal subjects. The two groups had similar ages, relative weights, smoking and dietary habits, and physical activities. The MI survivors had significantly higher concentrations of total and VLDL-triglyceride and total and LDL-cholesterol than the control subjects. The differences in HDL-cholesterol, and total apolipoproteins A-1 and B were of borderline significance. HDL₂ was significantly lower and LDL₂ was higher in the MI survivors. There was no difference in HDL₃. The differences in lipoprotein subfractions could be ascribed to differences in cholesterol, phospholipid and proteins, but not in triglyceride. The data suggest that the minor HDL₂ subfraction shows a closer association with established coronary heart disease than does total HDL-cholesterol. The increased LDL-cholesterol concentration in the MI survivors can be ascribed at least partly to an increase in the major subfraction, LDL₂.     

Effect of different insulin regimens on plasma lipoprotein and apolipoprotein concentrations in patients with non-insulin-dependent diabetes mellitus

The effect of insulin treatment with 2 different insulin regimens on the plasma concentrations of lipoproteins and apolipoproteins A1 and B was studied in 10 patients with non-insulin-dependent diabetes mellitus (NIDDM) and secondary failure to oral hypoglycaemic agents. The investigation was performed as a randomized crossover study with treatment periods of 8 weeks. Insulin was given either as mainly intermediate acting insulin before breakfast and dinner (2-dose insulin) or as regular insulin preprandially with intermediate acting insulin at bedtime (4-dose insulin). A similar improvement in glycaemic control was obtained with both insulin regimens. On treatment with oral agents the patients were found to have higher total plasma triglycerides and lower plasma high density lipoprotein (HDL) cholesterol than a matched non-diabetic control group. Insulin treatment almost completely normalized these lipid disturbances by reducing mean total plasma triglycerides with 36% and increasing plasma HDL cholesterol with 20% on 2-dose and 17% on 4-dose. The triglyceride concentration in the very low density lipoprotein (VLDL) fraction was reduced. Mean plasma low density lipoprotein (LDL)-cholesterol was not affected by any treatment. There was an increase of similar magnitude in both HDL2 and HDL3 concentrations but only the change in the HDL3 subfraction was statistically significant. Mean plasma apolipoprotein A1 concentration increased with 9% (P less than 0.05) while there was no significant change in the plasma apolipoprotein B concentration. The changes in the plasma concentrations of lipoproteins and apolipoproteins A1 and B were almost identical on 2- and 4-dose insulin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of adding fenofibrate (200 mg/day) to simvastatin (10 mg/day) in patients with combined hyperlipidemia and metabolic syndrome

Combined hyperlipidemia predisposes subjects to coronary heart disease. Two lipid abnormalities--increased cholesterol and atherogenic dyslipidemia--are potential targets of lipid-lowering therapy. Successful management of both may require combined drug therapy. Statins are effective low-density lipoprotein (LDL) cholesterol-lowering drugs. For atherogenic dyslipidemia (high triglycerides, small LDL, and low high-density lipoprotein [HDL]), fibrates are potentially beneficial. The present study was designed to examine the safety and efficacy of a combination of low-dose simvastatin and fenofibrate in the treatment of combined hyperlipidemia. It was a randomized, placebo-controlled trial with a crossover design. Three randomized phases were employed (double placebo, simvastatin 10 mg/day and placebo, and simvastatin 10 mg/day plus fenofibrate 200 mg/day). Each phase lasted 3 months, and in the last week of each phase, measurements were made of plasma lipids, lipoprotein cholesterol, plasma apolipoproteins B, C-II, and C-III and LDL speciation on 3 consecutive days. Simvastatin therapy decreased total cholesterol by 27%, non-HDL cholesterol by 30%, total apolipoprotein B by 31%, very low-density lipoprotein (VLDL) + intermediate-density lipoprotein (IDL) cholesterol by 37%, VLDL + IDL apolipoprotein B by 14%, LDL cholesterol by 28%, and LDL apolipoprotein B by 21%. The addition of fenofibrate caused an additional decrease in VLDL + IDL cholesterol and VLDL + IDL apolipoprotein B by 36% and 32%, respectively. Simvastatin alone caused a small increase in the ratio of large-to-small LDL, whereas the addition of fenofibrate to simvastatin therapy caused a marked increase in the ratio of large-to-small LDL species. Simvastatin alone produced a small (6%) and insignificant increase in HDL cholesterol concentrations. When fenofibrate was added to simvastatin therapy, HDL cholesterol increased significantly by 23%. No significant side effects were observed with either simvastatin alone or with combined drug therapy. Therefore, a combination of simvastatin 10 mg/day and fenofibrate 200 mg/day appears to be effective and safe for the treatment of atherogenic dyslipidemia in combined hyperlipidemia.     

The effects of prednisone therapy on plasma lipoproteins and apolipoproteins: a prospective study

The effect of prednisone therapy on plasma lipoproteins and apolipoproteins A-I, A-II, and E levels was studied prospectively in a heterogeneous group of six male and six female subjects. All patients were in a good general condition. The patients had normal hepatocellular, renal, and thyroid functions. During the first month of therapy, the following changes were noted: Plasma triglyceride (TG) levels increased slightly in female patients only. In the entire group, plasma cholesterol level increased (17.3% of initial value, P less than 0.01). Plasma high-density lipoprotein cholesterol (HDL-C) level increased by 68% (P less than 0.001), while plasma low-density lipoprotein cholesterol (LDL-C) level increased by only 10.9% (not significant), resulting in an increased ratio of cholesterol in the two (P less than 0.01). No change in levels of plasma apolipoproteins A-I, A-II, and E was evident. The ratio of HDL-C to plasma apolipoprotein A-I increased (P less than 0.01), indicating an increased lipid to protein ratio for this lipoprotein. Most of these changes were already apparent and significant 48 hours after initiation of treatment and persisted throughout the follow-up period (up to 18 months in some patients). Our results show that in patients with no major metabolic abnormality, prednisone induces significant changes of the lipoprotein system, especially in HDL.     

Effects of insulin on hypercholesterolemia in the streptozotocin-induced diabetic rats fed a high cholesterol diet

The effect of dietary cholesterol (Ch) on plasma lipoprotein and apolipoproteins (apo) in diabetic rats was investigated. Ch-fed diabetic rats were severely hypercholesterolemic and hypertriglyceridemic. They had higher concentrations of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL). Concentration of high density lipoprotein (HDL) was decreased. beta-VLDL increased predominantly in Ch-fed diabetic rats, whereas IDL increased in the Ch and propylthiouracil-fed control rats. According to sodium dodecyl sulfate polyacrylamide gel electrophoresis, VLDL and IDL from Ch-fed diabetic rats were unusual in that they contained more apo E, A-I and A-IV. Concentrations of plasma apo A-I and apo E were measured by radioimmunoassay. The diabetic rats fed a labo chow showed a significantly lower concentration of plasma apo E than control rats. Plasma apo E was extremely higher in the diabetic rats fed a cholesterol diet. Plasma apo A-I was significantly increased in the diabetic rats fed a labo chow and those fed a cholesterol. Insulin treatment significantly decreased the concentrations of VLDL, IDL and LDL and plasma concentration and distribution of apolipoproteins in lipoprotein subfractions changed toward normal. However, decreased HDL in the Ch-fed diabetic rats was not recovered by insulin treatment.     

High density lipoprotein subfractions and postheparin plasma lipases in alcoholic men before and after ethanol withdrawal

Serum lipoproteins (VLDL, LDL, HDL₂ and HDL₃) and postheparin plasma lipase activities were measured in 10 male alcoholic subjects at the end of a long drinking period and subsequently after 8 and 15 days of complete abstinence. None of the patients showed any clinical or histological evidence of cirrhosis or other alcoholic liver disease. Reference data were obtained from healthy normolipidemic nonalcoholic men of similar age. In spite of the heavy alcohol intake the serum triglyceride and VLDL triglyceride concentrations of the alcoholics were not different from those of the reference group. On the other hand, the LDL cholesterol of the alcoholics was remarkably low and did not rise significantly during the 2 wk of abstinence. The mean HDL cholesterol concentration of the alcoholic men was 54% higher than that of the controls. This was mainly due to elevation of HDL₂ (+63%) but also the HDL₃ cholesterol was higher than that of the control subjects (+20%). The phospholipid and protein concentrations of HDL₂ and the phospholipid of HDL₃ were also significantly increased in the alcoholic men in comparison with the controls. The composition of HDL subfractions of the alcoholics was only slightly abnormal with an increase of phospholipid and decrease of protein content of HDL₃. The concentration and composition of the HDL's returned to normal 1 wk after alcohol withdrawal. The postheparin plasma lipoprotein lipase and hepatic lipase activities of the alcoholic men were significantly higher than the respective values of the reference group. During eight off-alcohol days both enzyme activities decreased and reached the normal range. At the end of the drinking period no correlation was present between the levels of total HDL or its subfractions on the hand and any of the two lipase activities on the other. On the 8th off-alcohol day the HDL₂ phospholipid showed a highly significant positive correlation with lipoprotein lipase activity. It is concluded that the elevation of HDL during chronic use of alcohol in mainly due to increased concentration of HDL₂ and that this may be partly explained by an increase of lipoprotein lipase activity but that other mechanisms may also be involved. The low LDL concentration in alcoholic men without manifest liver disease is an interesting finding which should be studied further.     

Adrenocorticotrophic hormone exerts marked lipid-lowering effects in simvastatin-treated patients

OBJECTIVE: Recently, it was reported that treatment with adrenocorticotrophic hormone (ACTH) has a strong lipid-lowering effect in healthy individuals. The mechanism behind this has not been established. The aim of the present investigation was to study the effect of ACTH on the plasma lipoprotein pattern in patients treated with a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor. DESIGN: The ACTH treatment was given to 10 patients who were on long-term treatment with simvastatin 40 mg daily. ACTHI-24 was administered at the dose of 1 mg daily for four consecutive days. Blood samples for analyses of lipids, lipoproteins and apolipoproteins were collected before and after treatment. Second baseline was obtained 2 weeks after the end of treatment. RESULTS: The serum concentrations of cholesterol, triglycerides, low density lipoprotein (LDL) cholesterol, apolipoprotein B and lipoprotein(a) fell significantly by 16, 23, 23, 10 and 38%, respectively. The serum apolipoprotein E concentration increased significantly by 39%; the fraction that was not associated with apolipoprotein B increased by 47% whereas the fraction that was did not change significantly. There were no changes in the serum concentrations of high density lipoprotein (HDL) cholesterol and apolipoprotein AI. At the second baseline, the lipid variables had generally returned to previous levels. CONCLUSIONS: In patients on long-term simvastatin treatment, ACTH had marked lowering effects on the lipoproteins that contain apolipoprotein B. Moreover, the serum apolipoprotein E concentration increased significantly in response to ACTH treatment.     

Influence of bezafibrate,fenofibrate, nicotinic acid and etofibrate on plasma high-density lipoprotein levels

Increased levels of plasma high-density lipoprotein (HDL) cholesterol have been described after exposure to different dietary (such as ethanol) and environmental (such as chlorinated pesticides) factors as well as intense physical training. Several lipid-lowering drugs have also been shown to elevate HDL cholesterol. These findings are of particular interest, because adult levels of the putatively protective lipoprotein fraction appear not to be regulated by genetic factors.Four hypolipidemic drugs are herein considered, all of which reportedly elevate HDL cholesterolemia. Two of them, bezafibrate and fenofibrate, belong to the class of “fibrate” derivatives; nicotinic acid (NA) and etofibrate (E) show some similarities, E being the chemical association between nicotinic acid and clofibrate. In most studies, bezafibrate (B), with a very short half-life (2.1 hours), has induced an HDL cholesterol elevation of about 20%, both in types II and IV hyperlipidemic patients; it is controversial whether HDL₂ rather than HDL₃ levels are elevated by B. Fenofibrate (F) shows prolonged plasma half-life in man (>21 hours) and markedly increases HDL cholesterol levels, particularly in type IV patients; data are less homogeneous in type IIA and IIB cohorts. It appears that F may increase apoprotein C-II levels in very low density lipoproteins, possibly an index of stimulated lipoprotein lipase activity. Both B and F may behave as “catabolic agents,” stimulating the breakdown of triglyceride-rich lipoproteins and the transfer of surface components (free cholesterol) to HDL. A different case may be that of NA, which prevents the decrease of HDL cholesterol induced by carbohydrate-rich diets in volunteers. NA reduces the catabolism of HDL and markedly increases (300% or more) the $\text{HDL}{}_2\text{HDL}{}_3$ ratio in both volunteers and type IV patients, but not in type IIB patients. Whether, in addition to a “sparing” action on HDL, NA may also increase HDL levels by stimulating lipoprotein lipase activity is being disrupted. Finally, E may increase HDL cholesterol by 10% or more while exerting significant hypocholesterolemic activity. This compound is of interest because it may stimulate the release of prostacyclin from the arterial wall; prostacyclin may be derived from HDL phospholipids, unusually rich in arachidonic acid. This observation may offer another clue to the understanding of the mode of arterial protection exerted by HDL.     

An omega-3 polyunsaturated fatty acid concentrate increases plasma high-density lipoprotein 2 cholesterol and paraoxonase levels in patients with familial combined hyperlipidemia

A remarkable reduction of plasma concentrations of high-density lipoproteins (HDL), especially of the HDL(2) subfraction, is one of the typical lipoprotein alterations found in patients with familial combined hyperlipidemia (FCHL). Fourteen FCHL patients received 4 capsules daily of Omacor (an omega-3 polyunsaturated fatty acid [omega3 FA] concentrate providing 1.88 g of eicosapentaenoic acid [EPA] and 1.48 g of docosahexaenoic acid [DHA] per day; Pronova Biocare, Oslo, Norway) or placebo for 8 weeks in a randomized, double-blind, crossover study. Plasma triglycerides were 44% lower, and LDL cholesterol and apoliporpotein (apo)B were 25% and 7% higher after Omacor than placebo. HDL cholesterol was higher (+8%) after Omacor than placebo, but this difference did not achieve statistical significance. Omacor caused a selective increase of the more buoyant HDL(2) subfraction; plasma HDL(2) cholesterol and total mass increased by 40% and 26%, respectively, whereas HDL(3) cholesterol and total mass decreased by 4% and 6%. Both HDL(2) and HDL(3) were enriched in cholesteryl esters and depleted of triglycerides after Omacor. No changes were observed in the plasma concentration of major HDL apolipoproteins, LpA-I and LpA-I:A-II particles, lecithin:cholesterol acyltransferase (LCAT), and cholesteryl ester transfer protein (CETP). The plasma concentration of the HDL-bound antioxidant enzyme paraoxonase increased by 10% after Omacor. Omacor may be helpful in correcting multiple lipoprotein abnormalities and reducing cardiovascular risk in FCHL patients.     

Efficacy of sequential hormone replacement therapy in the treatment of hypercholesterolemia among postmenopausal women

Abstract. Objectives. To test the efficacy of hormone replacement therapy (HRT) and dietary therapy, compared to dietary therapy, in lowering LDL cholesterol levels among postmenopausal women. Design. A prospective parallel randomized study of sequential 17β-oestradiol and norethisterone acetate or placebo for 48 weeks. Setting. A University outpatient lipid clinic. Subjects. A total of 76 postmenopausal women, aged 43–60 years, with LDL cholesterol level ≥ 4.2 mmol I^?1 treated with a lipid-lowering diet. Main outcome measures. Levels of lipids, lipoproteins, apolipoproteins, fibrinogen and glucose tolerance. Results. Adherence to the diet was similar in both groups. Total and LDL cholesterol levels were reduced by 14% (95% CI, 11–17%) and 19% (95% CI, 14–23%), respectively, in the HRT group vs. 3% (95% CI. 0–7%) and 5% (95% CI, 0–11%) in the diet group. HRT reduced the levels of apolipoprotein B and lipoprotein(a). Levels of HDL cholesterol, HDL₂, HDL₃, triglycerides, lipoprotein populations and apolipoproteins. AI and AII remained unchanged. No adverse effects on glucose tolerance or on fibrinogen levels were observed. The reduction in LDL cholesterol was positively correlated with initial levels of LDL cholesterol and negatively correlated with body mass index. Conclusions. HRT is effective in reducing elevated LDL cholesterol levels, and should be considered in the treatment of hyperlipidaemic postmenopausal women, in addition to dietary therapy.     

Abnormalities in lipoprotein metabolism in Gaucher type 1 disease

We have previously described an association between Gaucher type 1 disease and reduced levels of total, low density lipoprotein (LDL), and high density lipoprotein (HDL) cholesterol. Plasma concentrations of apolipoprotein B and apolipoprotein AI were reduced in these subjects, while plasma apolipoprotein E (apoE), which can be synthesized and secreted by macrophages, was increased. To study the pathophysiologic basis for these changes in lipoprotein and apolipoprotein levels, we studied very low density lipoprotein (VLDL), LDL, and HDL metabolism in-depth in four subjects with Gaucher disease. Gel filtration of their plasma revealed that apoE was present in essentially a single population of lipoproteins in the large HDL range. In subject no. 4, studied presplenectomy and post-splenectomy, plasma apoE levels fell after surgery in association with a redistribution of apoE among the plasma lipoproteins to a pattern seen in normal subjects. Determination of the rates of secretion and catabolism of VLDL apoB and triglyceride were within normal limits. The reduced plasma levels of LDL and HDL cholesterol, and of both plasma apoB and apoAI, were associated with increased fractional catabolic rates of these apolipoproteins in LDL and HDL. These results indicate that the hypocholesterolemia present in subjects with Gaucher type 1 disease is associated with increased fractional catabolism of LDL and HDL. These findings, together with the evidence for alternations in plasma apoE metabolism in this disorder, suggest a role for the macrophage as the basis for these abnormalities.     

Serum lipids and apolipoproteins in children with Type 1 (insulin-dependent) diabetes during the first two years of the disease

Summary Serum lipoproteins and apolipoproteins were studied at diagnosis and 6,12 and 24 months later in 30 consecutive children aged 3–15 years with newly detected Type 1 (insulin-dependent) diabetes mellitus (December 1982–October 1984) and in 44 healthy control children. Serum triglycerides at diagnosis were significantly higher than after 6–24 months and also higher than in the control group (p<0.001). At follow-up, triglycerides in the very low density lipoproteins and low density lipoproteins were restored to normal, while high density lipoprotein triglycerides remained high. Serum cholesterol at onset of diabetes was significantly higher than in the control children (p<0.01), mainly because of increased very low density lipoprotein cholesterol (p<0.001). Cholesterol in serum and in the serum lipoprotein fractions was similar to that in the control children at follow-up, except that high density lipoprotein cholesterol was higher in the diabetic children after 6 months. The concentrations of the serum apolipoproteins A-I, A-II and B were higher at onset of diabetes than in the control children (p<0.001, p<0.01, p<0.05 respectively), with a significantly increased ratio of apolipoprotein A-I to A-II in the diabetic children (p<0.001). The serum apolipoprotein concentrations were normalised during treatment. The ratio of apolipoprotein A-I to B did not differ from that in control children. On admission, there were strong positive correlations between HbA_1c and the concentrations of the very low density lipoproteins and the low density and high density lipoprotein triglycerides. There were also significantly positive correlations (p<0.01) between HbA_1c and apolipoprotein A-I and apolipoprotein B respectively. After treatment these correlations disappeared, except for a positive correlation with very low density lipoprotein triglycerides at 2 years. In conclusion, at diagnosis, when the diabetic children were in an insulin-deficient state, all apolipoproteins and serum lipoprotein fractions, except cholesterol in high density lipoproteins and low density lipoproteins were increased. During the first two years of treatment the concentrations of lipoproteins and apolipoproteins in serum are similar to those in healthy children.     

Serum and urinary lipoproteins in the human nephrotic syndrome: evidence for renal catabolism of lipoproteins

The urinary excretion of lipoproteins and the possibility of catabolic alterations on glomerular filtration were investigated in four nephrotic subjects differing in etiology, serum lipoprotein profile, and 24 hr urinary output of protein and lipids. The apolipoproteins and lipoproteins of urine were compared with those of serum with respect to distribution profile, physical properties, and composition. Lipoprotein particles resembling the serum very low, intermediate, low, and high density lipoproteins (VLDL, IDL, LDL, and HDL, respectively) in density, particle size, and morphology were isolated from the urine. As expected from molecular sieving effects during glomerular filtration, the urinary HDL were more abundant than the lower density lipoproteins even when the plasma LDL was elevated markedly. However, little sieving effect was seen within the urinary HDL, which comprised a broad spectrum of particle sizes including the larger HDL₂, whose average diameter was similar to that of the plasma HDL. A sieving effect was not seen in the urinary LDL, except for a greatly increased proportion, about 20% of total particles, of HDL-like species. Intact apolipoproteins were not found in the concentrated urinary fraction isolated by ultrafiltration between the limits of 10⁴ and 5 × 10⁴ daltons. On the basis of immunoreactivity, gel electrophoresis, and amino acid composition, apolipoproteins B and AI are the major and minor proteins, respectively, of urinary LDL, and apo B is the major protein of the urinary IDL and VLDL. Apolipoproteins AI, AII, CI, CIII, and possibly AIV were isolated from the urinary HDL. As much as 20% of the protein moiety of the urinary HDL appeared to be large apolipoprotein fragments with molecular weights and isoelectric points similar to those of apo CII and apo CIII. The fragments were derived in part from apo AI, the least acidic form of which was lost preferentially. The lower density classes of urinary lipoproteins also appeared to have lost apo E and apo C's and to have undergone partial proteolysis. Apparently, the surface-exposed, readily exchangeable apolipoproteins are subject to proteolytic degradation upon glomerular filtration.     

Effects of prazosin and propranolol on blood pressure and plasma lipids in patients undergoing chronic hemodialysis

Twenty patients receiving hemodialysis who had mild to moderate hypertension were treated with prazosin or propranolol to control predialysis hypertension. Effective blood pressure control was achieved with prazosin (mean dose 8.3 ± 2.2 mg [± standard error of the mean], n = 10) and propranolol (mean dose 123 ± 39 mg, n = 10). Therapy with prazosin did not significantly affect total plasma triglyceride or total cholesterol levels. The level of high-density lipoprotein (HDL) cholesterol tended to increase, but not significantly. However, the HDL₃ subfraction did increase significantly, from 16.3 ± 1.5 to 20.6 ± 1.5 mg/dl (p = 0.05). Propranolol therapy increased plasma triglyceride levels, primarily of the very low density lipoprotein class. HDL cholesterol levels decreased from 44.2 ± 6.7 to 34.7 ± 4.2 mg/dl (p < 0.03). The reduction in the HDL cholesterol levels was attributable to a decrease in HDL₂ cholesterol levels (from 21.3 ± 3.8 to 16.3 ± 3.0 mg/dl, p < 0.04) and HDL₃ cholesterol levels (from 23.0 ± 3.1 to 19.5 ± 2.1 mg/dl, difference not significant). Thus, both prazosin and propranolol are effective in controlling hypertension in patients undergoing hemodialysis. HDL₃ cholesterol levels increased in patients treated with prazosin, but no other significant changes in the plasma lipids occurred. Patients treated with propranolol had a significant decrease in plasma HDL₂ and HDL₃ cholesterol levels.